Ch 4: Neural Conduction & Synaptic Transmission

This chapter is about introducing the function of neurons◦ How they conduct & transmit electrochemical

signals through the nervous system

Function of neurons centers around the membrane potential◦ The difference in electrical charge between the

inside & outside of the cell Can measure membrane potential using a

microelectrode◦ Measure the charge inside the cell & the charge

outside.

Resting Membrane Potential

A neuron’s resting potential is -70mV◦ Meaning, the charge inside the cell is 70mV less

than the charge outside◦ Inside < Outside

Because this value is beyond 0, it is said to be polarized

So at rest, neurons are polarized.

Resting Potential

It is polarized due to the arrangement of ions◦ The salts in neural tissues separate into + and –

charged particles called ions 4 main ions are responsible:1. K+ (potassium)2. Na+ (sodium)3. Cl- (chloride)4. - charged proteins

Ionic Basis

The ratio of – to + ions is greater inside a neuron than out, so you have a more – charge inside◦ Again, why the neuron’s resting potential is

polarized 2 things cause this imbalance & 2 things try

to equalize (homogenize)

Ionic Basis

Equalizers (homogenizers)1. Random motion2. Electrostatic pressure Cause imbalance1. Passive flow2. Active transport

Contributing Factors to Resting Potential

1. Random Motion Ions are in constant random motion Tend to be evenly distributed because

they move down their concentration gradient

◦ Move from areas of higher concentration to lower concentration

2. Electrostatic Pressure Ions with the same charge will repel each

other Opposite charges attract

Equalizers

Concentrations of Na+ and Cl- are greater outside the neuron (extracellularly)

K+ concentration is greater inside the cell (intracellularly)

Negatively charged proteins generally stay inside the neuron

Contributing Factors to Resting Potential

1. Passive Flow◦ Does not require energy◦ The membrane is selectively permeable to the

different ions K+ and Cl- ions easily pass through the membrane Na+ ions have difficulty passing through

◦ Ions passively flow across the membrane via ion channels

Special pores in the membrane

2. Active transport◦ Needs energy to power the pumps

Imbalance…rs

2. Active transport◦ Requires energy to power the pumps that

transport the ions◦ Discovered by Hodgkin & Huxley

Nobel prize winning research Why is there high Na+ and Cl- outside and high K+

inside? Why are they not passively flowing down their concentration gradients & reaching equilibrium?

Calculated the electrostatic pressure (mV) that would be necessary to counteract the passive flow down the concentration gradient (aka keep the concentrations uneven across the membrane) & how this differed from the actual resting potential

Imbalance…rs

Discovered that there are active pumps that counteract the passive flow of ions in & out of the cell (specifically for Na+ and K+)

Sodium-potassium pumps◦ Actively (using energy) pumps Na+ out & K+ in◦ 3 Na+ ions out for every 2 K+ ions pumped in

Other types of active transporters also exist

*Summary Table 4.1 (pg. 79)*

Active pumps cont.

Remember: At a synapse, the presynaptic neuron releases NT that bind with receptors on the postsynaptic neuron, to transmit the signal from one neuron to the next

When the NT bind with the postsynaptic neuron, they have either of 2 effects

1. Depolarize the membrane◦ Decrease the resting potential◦ **this means become less negative, aka approach zero**

2. Hyperpolarize the membrane◦ Increase the resting potential◦ ** make it more negative; further from zero**

Postsynaptic Potentials

-70 MV

0 MVhyperp

ola

rize

depola

rize

Postsynaptic depolarizations:◦ Excitatory postsynaptic potentials◦ EPSPs◦ Increase the likelihood that the neuron will fire

Postsynaptic hyperpolarizations:◦ Inhibitory postsynaptic potentials◦ IPSPs◦ Decrease the likelihood that the neuron will fire

Graded responses◦ Weak signals cause small PSPs; strong signals

cause large PSPs

Postsynaptic Potentials

Travel passively◦ Very rapid (practically instantaneous)

Like a cable◦ Deteriorate over distance

Lose amplitude as they go along Fade out Like sound

PSPs

Individual PSPs have almost no effect on getting a neuron to fire

However, neurons can have thousands of synapses on them & combining the PSPs from all of those can initiate firing◦ Called integration◦ Add all the EPSPs + IPSPs◦ Remember:

PSPs are graded & have different strengths ExcitatoryPSPs increase the likelihood of firing &

InhibitoryPSPs decrease the likelihood

Integration of PSPs

Neurons integrates PSPs in 2 ways

1. Over space: spatial summation

◦ EPSP + EPSP = big EPSP◦ EPSP + IPSP = 0 (cancel each

other out; assuming of equal strength)

◦ IPSP + IPSP = big IPSP

2. Over time: temporal summation

◦ 2 PSPs in rapid succession coming from the same synapse can produce a larger PSP

Integration of PSPs

If the sum of the PSPs reaching the axon hillock area at any one time is enough to reach the threshold of excitation, an action potential is generated ◦ The threshold is -65mV

So the resting membrane potential must be depolarized 5mV for the neuron to fire

Action potential◦ Massive, 1ms reversal of the membrane

potential -70 to +50mV

◦ Not graded; they are all-or-nothing responses Either fire at full force or don’t fire at all

Action Potentials

APs are generated & conducted via voltage-activated ion channels

When the threshold of excitation is hit, the voltage-activated Na+ channels open & Na+ rushes in

The Na+ influx causes the membrane potential to spike to +50mV

This triggers the voltage-gated K+ channels to open & K+ flows out

After 1ms, Na+ channels close End of rising phase

Conduction of APs

Beginning of repolarizing phase◦ K+ continues to flow out until the cell has been

repolarized; then the K+ channels close Cell returns to baseline resting membrane

potential

Conduction of APs cont.

Refractory Periods For about 1-2ms after the AP, it is

impossible to fire another one◦ Absolute refractory period

Followed by a period during which another AP can be fired, but it requires higher than normal levels of stimulation◦ Relative refractory period

Afterwards, the neuron returns to baseline & another AP can be fired as usual

Ions can pass through the membrane at the nodes of Ranvier between myelin segments

APs move instantly through myelinated segments to the next node, where concentrated Na+ channels allow the signal to be “recharged” and sent to the next

Conduction in Myelinated Axons

Saltatory Conduction Overall, this allows APs to be conducted much

faster than in unmyelinated axons, because the AP “jumps” from node to node and effectively “skips” the lengths covered in myelin (saltatory conduction)

Speed of conduction is faster with myelin Faster in thicker axons Ex: mammalian motor neurons are thick &

myelinated & can conduct signals at around 224 mph!!

Velocity of Axonal Conduction

Different types of synapses based on the location of the connection on each neuron◦ Axodendritic

“Normal” synapses Terminal button of axon on Neuron1 to

dendritic spine of Neuron2◦ Axosomatic

Axon of N1 to soma of N2◦ Dendrodendritic◦ Axoaxonic

Structure of Synapses

2 categories of NTs◦ Large:

Neuropeptides◦ Small:

Made in terminal buttons & stored in vesicles

Neurotransmitters

NTs are released via exocytosis At rest, NTs are in vesicles near membrane of

presynaptic neurons When an AP reaches the terminal button,

voltage-activated Ca2+ channels open & Ca2+ rushes in◦ Ca2+ causes the vesicles to fuse with the

membrane & release contents into the synaptic cleft

Release of NTs

NTs released from the presynaptic neuron cross the cleft & bind to receptors on the postsynaptic neuron

Receptors contain binding sites for only certain NTs

Any molecule that binds is a ligand There are often multiple receptors that

allow one kind of NT to bind: receptor subtypes◦ Different subtypes can cause different reactions

Activation of Receptors by NTs

There are 2 general types of receptors1. Ionotropic

◦ NT binds & ion channel opens & ions flow through

◦ Immediate reaction

2. Metabotropic◦ NT binds & initiates a G-protein to trigger a

second messenger, which moves within the cell to create a reaction

◦ Slow, longer lasting effects◦ More abundant

Receptors

A special type of metabotropic receptor Located on the presynaptic neuron & bind

with NTs from its own neuron Function to monitor the # of NTs in the

synapse◦ If too few, signal to release more◦ Too many, signal to slow/stop release

Autoreceptor

In order to allow the synapses to be available to signal again, the extra NT in the synaptic cleft need to be “cleaned up” by:

Reuptake◦ Most of the extra NT are quickly taken back into the

presynaptic neuron by transporters to be repackaged in vesicles for future release

Enzymatic degradation◦ NTs in the cleft are broken down by enzymes◦ Ex: acetylcholine broken down by acetylcholinesterase◦ Even these pieces are taken back into the neuron &

recycled

Reuptake, Degradation & Recycling

Unique signal transmission alternative to traditional synapses

Called electrical synapses Narrow gaps between neurons connected by

fine tubes called connexins that let electrical signals pass

Very fast & allow communication in both directions

Not yet fully understood in mammalian systems

Gap Junctions

Amino Acid NTs Monoamine NTs Acetylecholine Unconventional/Misc. NTs Neuropeptides

Neurotransmitters

AAs are the building blocks of proteins Glutamate

◦ Most common excitatory NT in the CNS Aspartate Glycine GABA

◦ Most common inhibitory NT

Amino Acid NTs

2 groups with a total of 4 NTs in this class Catecholamines:1. Dopamine (DA)

◦ Made from tyrosine/L-Dopa

2. Norepinephrine (NE)◦ Made from dopamine

3. Epinephrine◦ Made from NE

Indolamines:4. Serotonin (5-HT)

◦ Made from tryptophan

Monoamines

Functions at neuromuscular junctions, in ANS & CNS

Extra is mostly broken down in the synapse; by acetylcholinesterase

Receptors for Ach are said to be cholinergic

Acetylcholine (Ach)

Act differently than traditional NTs Nitric oxide & carbon monoxide

◦ Gases that diffuse across the membrane, across the extracellular fluid & across the membrane of the next neuron

Endocannabinoids◦ Essentially, the brain’s natural version of THC

(main active chemical in marijuana)◦ Ex: annandimide

Unconventional/Misc. NTs

Don’t worry about the specific types Just know that they are another type of NT Generally large NTs

Neuropeptides

Pharmaceutical drugs generally affect synaptic in 2 ways◦ Agonists facilitate the effects of a NT

Can bind to a receptor & activate it like the NT would◦ Antagonists inhibit

Can bind to a receptor & block it so NTs cannot bind

Drugs & Synaptic Transmission

Acetylcholine has 2 types of receptors1. Nicotinic

◦ Many in the PNS between motor neurons & muscle fibers

◦ Ionotropic◦ Nicotine: agonist◦ Curare: antagonist (causes paralysis)◦ Botox: antagonist

2. Muscarinic◦ Many located in the ANS◦ Metabotropic◦ Atropine: antagonist, receptor blocker

Example

Endogenous◦ Compounds naturally made within the body◦ Ex: enkephalins & endorphins

The body’s endogenous opioids An exogenous opioid is morphine Opioids are analgesics (pain relievers)

Misc.